{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T06:56:29Z","timestamp":1785308189478,"version":"3.55.0"},"reference-count":52,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2020,12,16]],"date-time":"2020-12-16T00:00:00Z","timestamp":1608076800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100017011","name":"Chicago Biomedical Consortium","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100017011","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Searle Funds"},{"DOI":"10.13039\/100001032","name":"Chicago Community Trust","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001032","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01AI118257"],"award-info":[{"award-number":["R01AI118257"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U19AI135964"],"award-info":[{"award-number":["U19AI135964"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["K24AI04831"],"award-info":[{"award-number":["K24AI04831"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R21AI129167"],"award-info":[{"award-number":["R21AI129167"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["KL2TR002002"],"award-info":[{"award-number":["KL2TR002002"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,2,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>KPC-producing Klebsiella pneumoniae (KPC-Kp) isolates commonly co-harbour the aminoglycoside-modifying enzyme (AME) gene aac(6\u2019)-Ib, which encodes an AME that can confer resistance to some of the commercially available aminoglycosides. We sought to determine the influence of AAC(6\u2019)-Ib in KPC-Kp on the pharmacodynamic activity of aminoglycosides.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Six KPC-Kp clinical isolates, three with and three without aac(6\u2019)-Ib, were analysed. Using these isolates, the bacterial killing of amikacin, gentamicin and tobramycin was assessed in static time\u2013kill experiments. The pharmacodynamic activity of the aminoglycosides was then assessed in a dynamic one-compartment infection model over 72\u2009h using simulated human pharmacokinetics of once-daily dosing with amikacin (15\u2009mg\/kg), gentamicin (5\u2009mg\/kg) and tobramycin (5\u2009mg\/kg).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>At clinically relevant aminoglycoside concentrations in time\u2013kill experiments and the dynamic one-compartment model, gentamicin was more active than amikacin or tobramycin against the isolates harbouring aac(6\u2019)-Ib. Amikacin, gentamicin and tobramycin all showed progressively reduced bacterial killing with exposure to repeated doses against most isolates in the dynamic one-compartment model. MIC values were generally not a good predictor of gentamicin pharmacodynamic activity against KPC-Kp, but were more reliable for amikacin and tobramycin.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Gentamicin may be preferred over amikacin or tobramycin for treatment of KPC-Kp infections. However, gentamicin MICs are not a consistent predictor of its pharmacodynamic activity and unexpected treatment failures are possible.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/jac\/dkaa480","type":"journal-article","created":{"date-parts":[[2020,10,30]],"date-time":"2020-10-30T20:12:52Z","timestamp":1604088772000},"page":"671-679","source":"Crossref","is-referenced-by-count":18,"title":["Optimizing aminoglycoside selection for KPC-producing <i>Klebsiella pneumoniae<\/i> with the aminoglycoside-modifying enzyme (AME) gene <i>aac(6\u2019)-Ib<\/i>"],"prefix":"10.1093","volume":"76","author":[{"given":"David A","family":"Butler","sequence":"first","affiliation":[{"name":"University of Illinois at Chicago College of Pharmacy, Chicago, IL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amisha P","family":"Rana","sequence":"additional","affiliation":[{"name":"University of Illinois at Chicago College of Pharmacy, Chicago, IL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fiorella","family":"Krapp","sequence":"additional","affiliation":[{"name":"Northwestern University Feinberg School of Medicine, Chicago, IL, USA"},{"name":"Instituto de Medicina Tropical Alexander von Humboldt, Universidad Peruana Cayetano, Lima, Peru"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3710-0497","authenticated-orcid":false,"given":"Shitalben R","family":"Patel","sequence":"additional","affiliation":[{"name":"University of Illinois at Chicago College of Pharmacy, Chicago, IL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2316-6727","authenticated-orcid":false,"given":"Yanqin","family":"Huang","sequence":"additional","affiliation":[{"name":"University of Illinois at Chicago College of Pharmacy, Chicago, IL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Egon A","family":"Ozer","sequence":"additional","affiliation":[{"name":"Northwestern University Feinberg School of Medicine, Chicago, IL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan R","family":"Hauser","sequence":"additional","affiliation":[{"name":"Northwestern University Feinberg School of Medicine, Chicago, IL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5396-911X","authenticated-orcid":false,"given":"Zackery P","family":"Bulman","sequence":"additional","affiliation":[{"name":"University of Illinois at Chicago College of Pharmacy, Chicago, IL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,12,16]]},"reference":[{"key":"2021021208590431100_dkaa480-B1","year":"2013"},{"key":"2021021208590431100_dkaa480-B2","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1016\/S1473-3099(13)70190-7","article-title":"Clinical epidemiology of the 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